Targeted therapies have been in the limelight as cancer therapeutics for the last few years. They have resulted in high response rates and improved overall survival in patients with cancer. However, consistent with other oncogene-targeted therapies, initial patient response is of limited durability and tumors eventually relapse.i 
The tumor microenvironment is increasingly recognized to play an important role in tumor proliferation, invasion, metastasis, and chemoresistance. It provides a conducive niche to the tumor through immunosuppression. Overcoming this immunosuppressive nature of the tumor microenvironment has been of particular interest in cancer therapy. Tumor cells manipulate the surrounding environment by producing cytokines that suppress cytolytic T-cells and recruit immunosuppressive cells.ii 
Colony stimulating factor 1 (CSF-1) is one such cytokine secreted by several cancer cell types. It induces the proliferation and differentiation of immunosuppressive myeloid cells such as M2 polarized macrophages and myeloid derived suppressor cells (MDSC) by binding to the CSF-1 receptor (CSF-1R) on cell surface.iii Cellular signalling mediated by colony-stimulating factor 1 (CSF1) and its receptor CSF-1R plays a critical role in monocyte differentiation and generation and activity of tissue-resident macrophages. The overexpression of CSF1 is associated with poor prognosis in breast, ovarian, and prostate cancer. Coincidentally, increased TAMs (tumor-associated macrophages) density also designates poor prognostic value, suggesting that CSF1-CSF1R axis may have an important role towards activity of TAMs.iv, v, vi 
The CSF1/CSF1R signalling pathway is targeted in the treatment against numerous malignancies, including breast, leukaemia, and glioblastoma. Studies have demonstrated that TAMs undergo turnover in a CSF-1R dependent manner, with continuous inhibition of the CSF-1R pathway being essential for depletion of TAMs and serving as an anticancer therapy. Therefore, the immunosuppressive tumor environment mediated by CSF-1 helps tumor cells escape killing by immune cells and assists them to metastasize. Since CSF-1R regulates the functioning of macrophages impacting tumor progression, inhibiting the CSF-1R pathway has emerged as a major therapeutic goal in cancer. Recently, some of the CSF-1R inhibitors had shown promising results in terms of potency, selectivity and bioavailability of cFMS kinase activity.vii 
Among them, one of the well-known inhibitor which is in the clinical phase trials is BLZ-945. Although high in potency, this inhibitor fail to achieve a sustained inhibition of CSF-1R and are associated with toxicity to normal cells. Accordingly, there remains an urgent need for CSF-1R inhibitors with an improved activity profile while exhibiting decreased toxicity.